Alzheimer's disease (AD) is the most common cause of dementia, a devastating disorder that affects over 35 million people worldwide. Our ultimate objective is to apply quantitative and systems pharmacology (QSP) approaches to AD drug discovery and development in order to deliver treatments capable of significantly attenuating the progression and/or preventing the disease. We will utilize this planning grant to integrate the necessary personnel, expertise and resources to assemble an infrastructure of cores across four San Diego medical research institutions (UCSD, the Salk Institute, the Scripps Research Institute and the Sanford Burnham Medical research Institute) and UCLA that are necessary for planning an AD Translational Center for Predictive Drug Development. This will be accomplished in part using a web-based platform that is currently under development (Systems Medicine Alzheimer's Research and Treatment or SMART) ://smart.ucsd.edu. Cataloging and integration of resources including cellular and animal models, reagents, chemical libraries of compounds, existing compounds in various stages of development, biosamples, postmortem brain tissue, methods such as high throughput screens and archiving and annotating of newly-generated multi-omics datasets (including existing data from cellular and animal models) as well as data from human longitudinal studies. A major focus will be the utilization of human iPSC (hiPSC) from extremely well phenotyped patients (including extreme phenotypes) to attempt to establish disease in a dish models. In addition we will capitalize on the local abundance of expertise in systems biology, biostatistics and bioinformatics bioengineering, pharmacology, neuropathology and clinical research to establish appropriate training programs in QSP for graduate students, medical trainees and postdoctoral scholars. Finally, we will identify processes to enable highly effective data sharing and establish strong collaborations with pharmaceutical companies.